Tetrahydrocurcumin Suppresses Bladder Carcinogenesis via Reprogramming O-GlcNAcylation-Phosphorylation Crosstalk

Tetrahydrocurcumin Suppresses Bladder Carcinogenesis via Reprogramming O-GlcNAcylation-Phosphorylation Crosstalk | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Tetrahydrocurcumin Suppresses Bladder Carcinogenesis via Reprogramming O-GlcNAcylation-Phosphorylation Crosstalk Mengni Yang, Rui Li, Mengting Zhou, Yu Dong, Junning Zhao, Ruirong Tan This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9394670/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Bladder cancer exhibits high recurrence rates and limited therapeutic options in advanced stages. Although post-translational modifications (PTMs) are critical regulators of tumor biology, their systems-level remodeling during bladder carcinogenesis remains insufficiently defined. Using a BBN-induced murine bladder cancer model combined with tumor-derived organoids and bladder cancer cell lines, we observed a consistent global elevation of protein O-GlcNAcylation across tumor-associated contexts. Site-resolved quantitative proteomics revealed that this increase reflected selective redistribution rather than uniform accumulation, with differential O-GlcNAc sites nearly evenly divided between up- and down-regulated events. Integrated analyses demonstrated preferential enrichment of up-regulated O-GlcNAcylation within cytoskeleton-adhesion modules and Notch-related domains, whereas down-regulated events were more closely associated with structural maintenance and homeostatic programs. Approximately half of differentially O-GlcNAcylated proteins exhibited concurrent phosphorylation changes, indicating coordinated multi-layer PTM remodeling. Pharmacological inhibition of O-GlcNAc transferase suppressed bladder cancer cell proliferation and organoid growth, supporting a functional association between elevated O-GlcNAcylation and tumor growth. Tetrahydrocurcumin (THC) reduced global O-GlcNAcylation and induced directional remodeling of BBN-associated O-GlcNAc patterns. Cross-comparative analyses identified subsets of sites exhibiting opposite regulation trends following THC intervention. Collectively, these findings define a spatially and functionally organized PTM remodeling landscape in bladder cancer and suggest that THC exerts anti-tumor effects in part through coordinated reprogramming of O-GlcNAcylation and phosphorylation networks. Cancer Biology Bladder cancer Post-translational modifications O-GlcNAcylation Phosphorylation Tetrahydrocurcumin Full Text Additional Declarations The authors declare no competing interests. Supplementary Files Supplementaryinformation.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9394670","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":621718578,"identity":"7956b98e-400d-4581-9a5a-98b8f507e30f","order_by":0,"name":"Mengni Yang","email":"","orcid":"","institution":"School of Pharmacy, Chengdu University of Traditional Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Mengni","middleName":"","lastName":"Yang","suffix":""},{"id":621718592,"identity":"c9facdbb-d312-4dde-a652-9810375d2209","order_by":1,"name":"Rui Li","email":"","orcid":"","institution":"Sichuan Cancer Hospital and 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